Tablets and capsules are the most common dosage forms for the oral administration of nutritional, medicinal, or other therapeutic products. It is well known, however, that these dosage forms are unacceptable for use by people who have difficulty in swallowing tablets and capsules and that the difficulty is exacerbated by larger tablets and capsules and, in some instances, by the bad taste of the medication. It is generally accepted that these types of problems with medications are serious because they may lead to a failure on the part of patients to comply with the medication regimen ordered by the physician.
The common alternatives to conventional tablets and capsules are chewable tablets and aqueous or hydroalcoholic liquids such as syrups, suspensions and elixirs. Such dosage forms are commonly used for analgesics, cough and cold medications, antibiotics, vitamins and many other nutritional or medicinal products. In general, these forms do not significantly improve the taste of a medication or make it easier to swallow larger doses.
Normally, therapeutic amines such as dextromethorphan, phenylpropanolamine, pseudoephedrine, chlorpheniramine, triprolidine, among others, are very bitter when used in therapeutic concentrations. Efforts to overcome or mask this bitterness have not been completely successful. An adsorbate marketed for this purpose is composed of dextromethorphan hydrobromide (10%) adsorbed on a substrate (90%) of magnesium trisilicate. When this adsorbate is used in therapeutic concentrations, the bitterness of DMHBr is significantly reduced, but it is still present. Other materials have been recommended for use as adsorption substrates: e.g., clays such as magnesium aluminum silicate (available under the trade name Veegum) and hydrous aluminum silicate (bentonite). Clathrates (such as cyclodextrins), sodium aluminum silicates (zeolites) and ion-exchange resins have all been mentioned for this use--i.e., to form adsorbates that will mask bitter tastes.
The formation of adsorbates is believed to be an adsorption process, an ion-exchange process, or both. Heretofore, it was believed that adsorbates using a clay substrate would only form in aqueous systems on the grounds that the clay must hydrate and swell before its adsorptive properties develop. It has never been suggested that such adsorbates could be formed in non-aqueous oil systems.
In general these substrates for taste masking are rather difficult to use successfully. The active-substrate complex must typically be prepared separately (as in the case of the dextromethorphan hydrobromide/magnesium trisilicate adsorbate) and then added "pre-formed" to the pharmaceutical dosage form--e.g., a chewable tablet or lozenge. Thus, the standard procedure for forming an adsorbate is to hydrate the adsorption substrate (e.g., a clay such as magnesium aluminum silicate) in hot water (60.degree. C.). The weight of the substrate is usually in the ratio of 10:1 to the drug. The drug, usually a HCl or HBr salt of an amine active therapeutic agent, is dissolved in sufficient hot water. The drug solution is added to the substrate suspension with high speed agitation. The entire mass will coagulate. The mass is then filtered, washed, dried and then pulverized to a fine powder. Drugs such as dextromethorphan HBr, pseudoephedrine HCl and phenylpropanolamine HCl can be adsorbed onto clays by this method, but the arduous nature of the procedure restricts its use.
Applicants' U.S. Pat. Nos. 4,639,367 and 4,752,465 describe stable, edible anhydrous aerosol foams comprising a foamable liquid oil, a foaming agent, a propellant and dispersed solid particles which may include active therapeutic agents. The foam is a stable whip having the consistency of whipped cream and can be dispensed in repeatable and measurable quantities onto a spoon. It is useful to dispense a wide variety of active therapeutic agents and serves as an alternative to tablets or capsules which are hard to swallow or liquid medicines having a bad taste. The substance of these patents is hereby incorporated by reference.
While the aerosol foams taught by these patents do not generally contain adsorbates, they are fully satisfactory for the masking of objectionable taste in most drugs, especially at low and medium therapeutic concentrations. However the extremely bitter taste of particular active therapeutic agents cannot be totally overcome or masked by this technique alone, especially when the agents are used at particularly high levels. The patents illustrate the use of an adsorbate to assist in overcoming such bitter tastes. Thus, Example 17 of U.S. Pat. No. 4,639,367 discloses the use of magnesium aluminum silicate in connection with the formation of a foam whip of trimethoprim (a urinary tract drug). Nonetheless, there remain particular amine active therapeutic agents of such extreme bitterness that, when employed at high concentrations, their bitter taste cannot be overcome, even by an aerosol foam in which the amine form of the drug is adsorbed on magnesium aluminum silicate as taught by these examples.
Accordingly, an object of the present invention is to provide a stable, edible anhydrous aerosol foam or whip which can mask the bitter taste of an amine active therapeutic agent, even at a high therapeutic concentration.
Another object is to provide such an aerosol foam which employs adsorbate technology without requiring pre-formation of the adsorbate.
A further object is to provide such an aerosol foam which may be easily and rapidly formed, creating a taste-masking adsorbate in situ.